Predictors of an earlier diagnosis of Autism Spectrum Disorder in children and adolescents: a systematic review (1987-2017).

Autism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder in which the first signs generally emerge at approximately 12 months of age but its diagnosis is feasible only from the age of 18 months. According to the literature, the average age of diagnosis ranges from 2.7 to 7.2 years, which raises the question of factors associated with early diagnosis as a condition for early intervention. In this systematic review, we aim to identify clinical, social, and environmental factors associated with the age at which the diagnosis of ASD is confirmed in children. A literature search was performed in the Pubmed, Web of Sciences, PsycInfo, and Cochrane databases. Among the 530 publications identified, 50 were selected according to the inclusion criteria. This review focuses on studies conducted in 21 countries using data collected over a period from 1987 to 2017. These studies were published before December 31st, 2019. The results suggest that the diagnosis of ASD occurs earlier if there is a delay in social communication or the presence of intellectual disability. There is a low level of evidence concerning associations between the age at diagnosis and sex, race, parental education, or socioeconomic status and accessibility to health care. Further studies using large and well-characterized data sets are needed to simultaneously explore clinical and socio-environmental factors involved in early diagnosis.

Perceptions of parents of the impact of autism spectrum disorder on their quality of life and correlates: comparison between mothers and fathers.

PURPOSE: To compare mothers and fathers perceptions of the impact of autism spectrum disorder on their Quality of Life (QoL), we used the Parental-Developmental Disorders-Quality of Life scale (Par-DD-QoL). METHOD: The perception of QoL of mothers and fathers was compared for 130 pairs of parents of children with ASD and the associated variables were investigated. RESULTS: Mothers perceived a significantly greater impact of ASD on their QoL than fathers. Parents perceived a higher impact of ASD on global QoL when their child's adaptive skills were low and when the level of aberrant behaviors was high. More precisely, the perception of QoL by the mothers was negatively associated with their child's internalized disorders, whereas the perception of QoL by the fathers was negatively associated with their child's externalized disorders. Neither the mothers' nor the fathers' perception of the impact on QoL was associated with their children's age or the severity of their autistic symptoms. Some parental factors, such as being members of a family association, having benefited from training in ASD and having experienced a disruption in professional activity were associated with a greater impact on their QoL. CONCLUSION: Our finding that the perceived impact of ASD on QoL differed between mothers and fathers argues for individualized psychosocial support. Moreover, the strong correlation between the child's clinical characteristics and the perception by parents of a higher impact of ASD on QoL should be seen as red flag concerning the needs of the parents in terms of social and educational support. TRIAL REGISTRATION NUMBER: NCT02625116 (October 2015).

A longitudinal exploratory study of changes in sensory processing in children with ASD from the ELENA cohort.

Atypical sensory processing (SP) is a diagnostic criterion of autism spectrum disorder (ASD). However, little is known about its course during development. In this exploratory longitudinal study, we aimed to investigate the course of SP among children with ASD and identify clinical variables associated with changes. We used a subsample of 51 children with confirmed ASD, aged from 3 to 10 years, recruited from the ELENA cohort. SP was assessed using the Sensory Profile questionnaire at baseline and three years later. Our preliminary results highlight the heterogeneity of the evolution of SP during the children's development and the existence of three subgroups based on the course of SP (improvement, stable, and worsening). In addition, the children's adaptive skills and maladaptive behaviors were related to the course of SP. These results could be confirmed in future studies with a larger sample size using a longitudinal approach to capture individual variability in SP. In addition, our results highlight the importance of accounting for temporal changes in the sensory needs of individuals with ASD in clinical practice.

Sensory processing related to attention in children with ASD, ADHD, or typical development: results from the ELENA cohort.

Autism-spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are early neurodevelopmental conditions that share clinical characteristics, raising important issues in clinical diagnosis. We aimed to compare (1) sensory processing in four groups of children: ASD alone, ASD + ADHD, ADHD alone, and typical development (TD) and (2) the association between sensory processing and attention in the three groups with neurodevelopmental disorders. Our sample included 120 children aged from 6 to 12 years divided into four groups: ASD alone (N = 43), ASD + ADHD (N = 18), ADHD alone (N = 28), and TD (N = 31). Atypical sensory processing was more frequent in ASD and/or ADHD than in TD, without a significant difference between ASD and ADHD. However, the variance analysis of attention problems revealed differences between the ADHD and ASD groups. Thus, the rate of atypical sensory processing was comparable between the ASD and ADHD groups, suggesting that further studies are needed to explore atypical SP in all neurodevelopmental disorders.

Impact of autism in adolescents on parental quality of life.

PURPOSE: To study the impact of autism spectrum disorders (ASDs) on parental quality of life (QoL) at adolescence using the parental-developmental disorders-quality of life scale (Par-DD-QoL). METHODS: One hundred and fifty-two mothers of adolescents with ASD completed Par-DD-QoL. This scale assesses the following dimensions: emotional, daily disturbance and global QoL. This cross-sectional study uses a subset of data collected at the final time of a follow-up study (EpiTED cohort). RESULTS: A polytomic regression identified an increase in aberrant behavior scores as the major independent risk factor for parental QoL. The identified protective factors were the increase in daily living, communication and object cognition scores and a higher number of siblings. CONCLUSIONS: Those results suggest that there is a negative effect of externalizing behaviors and a protective effect of adaptive skills, communication and object cognition on parental QoL. Study limitations and implications are discussed.

Dyadic Effect of Coping on the Perceived Impact of ASD of Children on Parental Quality of Life: Report from the ELENA Cohort.

Autism spectrum disorder (ASD) has a significant impact on the quality of life (QoL) of families. This study aimed to examine, for parents of children with ASD, the dyadic effect of each parent's coping strategy on the perception of the impact of ASD on their QoL. In total, 164 couples completed self-report questionnaires, including the Par-DD-QoL, to evaluate the parental perception of QoL. Results from the actor-partner interdependence model showed that, in addition to the effect of the mothers' and fathers' emotion-focused coping on their own perception of QoL, the mothers' emotion-focused coping plays a key role in the fathers' perception of QoL. These findings suggest that both parents of children with ASD would benefit from couple-focused interventions.

Changes in mothers' and fathers' stress level, mental health and coping strategies during the 3 years following ASD diagnosis.

BACKGROUND: ASD in a child affects parental mental health, with elevated levels of stress, anxiety and depression reported in parents. METHOD: In this study, we examined mothers' and fathers' stress, anxiety and depression, as well as their coping strategies in a sample of 103 children and adolescents enrolled in the ELENA cohort study in France at diagnosis and three years after diagnosis. RESULTS: Results showed that mothers had higher levels of stress and anxiety / depression than fathers and used more social support coping strategies at diagnosis, which might be explained by increased levels of parental involvement. Mothers' stress level significantly decreased during the three years following ASD diagnosis but no such decrease was observed in fathers' stress level. A significant decrease in anxiety and depression was observed for both parents, suggesting that parental distress is particularly elevated during the critical diagnosis period. Results finally yielded a significant decrease in emotion-focused coping strategy in mothers over the three-year period, an ineffective strategy that takes places at the time of diagnosis but then decreases during the period following ASD diagnosis, in relation to the acceptance process. CONCLUSIONS: Implications in terms of addressing the unmet mental health needs of parents and their coping strategies are discussed.

Clinical predictors of psychotropic medication prescription in children with ASD of the ELENA cohort.

Psychotropic drugs are often used to treat behavior problems in ASD with some evidence supporting efficacity (e.g.: risperidone and irritability) but also significant side effects at the short and longer-term. It is then essential to know better the factors associated with the prescription of these medications and potentially implement early behavioral and psychosocial intervention or cognitive remediation before to use medication. We designed a case-control study based on the population of the ELENA cohort to assess the factors associated with early psychotropic drugs use in children with ASD. Externalized behavior symptoms (measured by the Child Behavior Checklist) is the leading risk factor during the first years of follow-up (aOR = 2.8; CI [1.04; 7.67]; p = 0.04). Age, gender, autism severity, adaptive behaviors, or internalized behaviors were not associated with psychotropic medication prescription. Low IQ and parents who had received training tended to increase the risk of psychotropic medication prescription during follow-up but were not statistically significant. These findings underscore the need for early identification of symptoms of externalizing behaviour, early appropriate information for parents about treatment with and without medication, early analysis of externalising behaviour and targeted treatments.

Determinants of Inclusion in Mainstream School for Children with Autism Spectrum Disorders from the EpiTED Study: A 10-Year Follow-up Cohort.

Inclusion of students with Autism Spectrum Disorder (ASD) in mainstream schools has a positive impact on their social and daily living behaviors. Our objective was to identify clinical and socio-demographic variables promoting or limiting inclusion in mainstream school through childhood and adolescence. The EpiTED study is a long-term, prospective, multicenter cohort of 281 ASD children included before the age of 7, with a 10-year follow-up in France. Variables significantly linked to inclusion in mainstream school were identified using a mixed-effect logistic regression model: greater autonomy [OR = 1.45 (1.29-1.63)], lesser symptom severity [OR = 0.96 (0.92-0.99)] and fewer siblings [OR = 0.86 (0.75-0.99)]. In the multivariate model, the probability for a child of being included in mainstream school decreased over time [OR = 0.91 (0.85-0.97)], i.e. with age.

Multistage screening process for neurodevelopmental disorders in siblings of children with autism: the FRATSA protocol study.

INTRODUCTION: The elevated rates of neurodevelopmental disorders (NDDs) among siblings of children with autism spectrum disorder (ASD) raise concerns about their developmental monitoring and development. The main aim of this study is to assess the feasibility and acceptability of a standardised screening process on a large sample of siblings. METHODS AND ANALYSIS: This prospective study will assess the feasibility of a selective and multi-stage screening process for NDD performed on 384 siblings of children with confirmed ASD. Stage 1 will consist of the screening of NDD performed using online parental questionnaires (Social Responsiveness Scale, IdentiDys scale, DCDQ, parental concerns) through a web platform. In cases of a positive result, the second stage, consisting of a clinical semi-structured interview with a psychologist, will be proposed to the sibling before referral for diagnosis and treatment, if necessary. Approximately 12 months after stage 2, parents will be contacted by telephone to collect the diagnosis established following the referrals and their level of satisfaction concerning the screening process. Based on an expected participation rate of 50%, to estimate this rate with an accuracy of 5%, it is necessary to screen 384 subjects. ETHICS AND DISSEMINATION: The Ethics Committee on the Research of Human Subjects of Paris (Ile de France VII) approved this study in March 2022 (number: 2021-A02241-40). Express consent is required from all participants. Findings from the cohort study will be disseminated by publication of peer-reviewed manuscripts, presentations at scientific meetings and conferences with associated teams. TRIAL REGISTRATION NUMBER: NCT05512637.

Early risk factors for anxiety disorders in children with autism spectrum disorders: results from the ELENA Cohort.

Anxiety in children with autism spectrum disorder (ASD) negatively affects their social interactions, and quality of life. It is necessary to identify early risk factors for anxiety to tailor prevention and interventions. We aimed to examine the clinical level of anxiety in children with ASD from 5 to 10 years of age and identify potential early risk factors 3 years earlier. Participants were ASD children included in ELENA, a French prospective cohort. In this study, we used the collection of data at Time 1-T1 (at baseline) and Time 2-T2 (3 years after T1). Two groups were identified at T2 according to the threshold for anxiety on the CBCL: ASD-only group and ASD + anxiety group. Our results showed that half of the children in our sample had a clinical level of anxiety at T2. Regression analysis showed that greater ASD severity and lower sensory processing difficulties predicted lower anxiety, whereas higher levels of restricted and repetitive behaviours tended to predict higher levels of anxiety. The high prevalence of clinical-level anxiety in our sample suggests the need for specific assessment and targeted treatment of anxiety on a routine basis.

Sex-related differences in clinical characteristics of children with ASD without ID: Results from the ELENA cohort.

Objective: The literature on sex related-clinical differences for children with autism spectrum disorder (ASD) is highly contradictory, whereas this topic has major clinical implications. We aimed to investigate sex-related clinical differences in children with ASD without intellectual disability (ID). Materials and methods: We compared 319 boys and 65 girls with ASD without ID, aged from 2 to 12 years, recruited from a multiregional cohort on their clinical profiles based on the scores for the Vineland-II, the SRS-2, the ADOS calibrated severity score, sensory processing, aberrant behaviors, and comorbidity rates. Results: Our results confirm a high sex ratio of 4.9 males/females. Many similarities were found in the clinical profiles. However, we found that girls had higher SRS-2 total scores. In addition, there was a negative correlation between the SRS-2 total score and the intellectual quotient level (IQ) for girls only. Conclusion: We confirm the higher rates of boys with ASD without ID. A comparison between the girls and boys showed them to have similar clinical profiles, except for the SRS- 2 total scores, which were higher among girls, suggesting more severe social impairment perceived by parents. Our findings that the cognitive level is related to ASD severity in girls should be taken into account during the diagnostic procedure in the clinical interpretation of gold-standard measures of ASD, and additional clinical observations are necessary. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT02625116s].

Factors associated with age of diagnosis in children with autism spectrum disorders: Report from a French cohort.

LAY ABSTRACT: Autism spectrum disorder is an early onset neurodevelopmental disorder and diagnosis can be made as early as 18 months of age. Early diagnosis of autism spectrum disorder is critical as it leads to early intervention. Age of autism spectrum disorder diagnosis has been linked to the child profile as autism spectrum disorder is characterized by strong heterogeneity, but is also influenced by socio-economic factors. There is paucity of data on age of diagnosis of autism spectrum disorder in France. We therefore examined the age of autism spectrum disorder diagnosis in 554 children and adolescents enrolled in the ELENA cohort study with respect to the influences of child profile, family antecedents, and socio-economic factors. The mean age of diagnosis was 4.9 years (±2.8 years). Early diagnosis, before 3 years of age, was related to the co-occurrence of intellectual disability, higher autism spectrum disorder symptom severity, and lower communicative abilities. Children in low socio-economic status families tended to have an earlier diagnosis, but these children also had greater degree of intellectual impairment compared to children in high socio-economic status families. The age of autism spectrum disorder diagnosis was not associated with the presence of an older sibling with autism spectrum disorder. The observed current trend of an inverse relationship between socio-economic status and age of diagnosis of autism spectrum disorder suggests equitable access to autism spectrum disorder services in France where health coverage is universal and free. Better screening of more subtle/less severe forms of autism spectrum disorder is needed, as well as further assessment of the link between the co-occurrence of autism spectrum disorder and intellectual impairment in children in lower socio-economic status families.

Clinical characteristics of children with ASD and comorbid ADHD: Association with social impairment and externalizing and internalizing behaviours.

BACKGROUND: Autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are frequently occurring conditions that are often associated (ASD + ADHD). However, there are few comparative studies concerning the clinical presentation in patients formally diagnosed with both ASD and ADHD. Here, we aimed to 1) compare social impairment and externalizing/internalizing behavioural problems across four groups of children: ASD + ADHD, ASD alone, ADHD alone, and typical development and 2) examine their bidirectional relationship with ASD and/or ADHD symptoms. METHODS: This study included 186 participants from 6 to 12 years of age: single ASD (n = 98), ASD + ADHD (n = 29), single ADHD (n = 28), and TD (n = 31). RESULTS: The results showed that children in the ASD + ADHD and single ASD groups had a higher level of social impairment than those in the single ADHD group. In addition, children in the single ADHD group presented a greater attention deficit than those in the single ASD group. Externalizing /internalizing behaviours were more frequent in all groups with neuro-developmental disorders than in typical development. In addition, externalizing behavioural problems were related to ADHD severity in the ASD + ADHD and single ADHD groups, whereas internalizing behaviours were related to ASD severity. CONCLUSIONS: These findings highlight the specific needs of children who have both ASD and ADHD and underscore the necessity of individualizing their interventions.

WISC-V Profiles and Their Correlates in Children with Autism Spectrum Disorder without Intellectual Developmental Disorder: Report from the ELENA Cohort.

The intellectual functioning of people with autism spectrum disorder (ASD) without intellectual developmental disorder (IDD) has not been widely studied. However, marked heterogeneity in assessment measures, samples, and results has been an obstacle for the generalization of findings. We aimed to (a) describe WISC-V intellectual functioning in a sample of children with autism spectrum disorder without intellectual developmental disorder, (b) identify WISC-V profiles, and (c) explore whether WISC-V intellectual functioning is related to ASD symptom severity and adaptive skills. Our sample consisted of 121 children from 6 to 16 years of age with ascertained ASD without an intellectual developmental disorder (IDD). The intellectual functioning of the participants was within the average range. Intra-individual analysis showed that children with ASD performed better on visual than auditory working-memory tasks. Moreover, the intellectual functioning of the participants correlated negatively with ASD symptom severity but positively with adaptive communication skills. Overall, we identified six intellectual profiles according to verbal and reasoning skills. These findings highlight the relevance of WISC-V assessment for children with ASD without an IDD to individualize intervention, especially remediation. LAY SUMMARY: This study examined WISC-V intellectual functioning in 121 children with autism spectrum disorder (ASD) without an intellectual developmental disorder (IDD). We found their intellectual functioning to be within the average, as was that of their peers with typical development (TD), and their verbal and reasoning skills were the most discriminant. In addition, the better their intellectual functioning was, the better their adaptive communication skills and the less severe their ASD symptoms. These findings highlight the relevance of WISC-V assessment in ASD to individualize early psychological remediation. Autism Res 2021, 14: 997-1006. © 2020 International Society for Autism Research, Wiley Periodicals, LLC.

Association between residential proximity to agricultural crops and adaptive behaviors in children with autism spectrum disorder from the French ELENA cohort.

Influences of pesticide exposures on the clinical expression of children with ASD not known. The aim of this study was to analyze the associations between early residential proximity to agricultural crops, proxy of exposure to pesticides, and adaptive behaviors in children with ASD. Children with ASD were recruited within the Etude Longitudinale de l'Enfant avec Autisme (ELENA) French cohort. Adaptive behaviors were assessed with the second edition of the Vineland Adaptive Behavior Scales (VABS-II). Baseline subscores in communication, daily living skills and socialization were considered. Residential exposure to agricultural crops was estimated by crops acreage within a 1000m radius around homes. We ran multiple linear regression models to investigate the associations between exposures to agricultural crops during the pregnancy (n = 183), the first two years of life (n = 193) and adaptive behaviors in children with ASD. The mean (SD) age of children at the inclusion in the ELENA cohort was 6.1 (3.5) years, 39% of them presented an intellectual disability (ID). The mean communication score was 73.0 (15.8). On average, the crop acreage covered 29(27)% of the acreage formed by the 1000m radius around homes. Each increase of 20% in the crop acreage was associated with a significant decrease in communication score of the VABS-II in children without ID for the pregnancy (ß = -2.21, 95%CI: 4.16 to -0.27) and the first two years of life (ß = -1.90, 95%CI: 3.68 to -0.11) periods. No association was found in children with ID. This study opens perspectives for future works to better understand ASD phenotypes.

Association between prenatal and perinatal factors and the severity of clinical presentation of children with ASD: Report from the ELENA COHORT.

Many studies have suggested that prenatal and perinatal factors increase the risk for autism spectrum disorder (ASD). However, few reports have addressed the question of their influence on the severity of the clinical presentation of children with ASD. Our objective was to determine the prenatal and perinatal factors that are associated with the severity of autistic symptoms and intellectual and adaptive functioning deficits. Data were collected from a subset of 169 children with a confirmed diagnosis of ASD, recruited from the ELENA cohort. A risk of premature delivery was associated, with an increased risk for severe autistic symptoms and placental pathologies and birth complications were associated with an increased risk of communication adaptive deficits, in multivariate analysis. Our results highlight the importance of systematic screening for these pre/perinatal factors, especially in mothers at risk of having a child with ASD.

The French Version of the Revised Ritvo Autism and Asperger Diagnostic Scale: A Psychometric Validation and Diagnostic Accuracy Study.

The early recognition of ASD in adults is challenging, in particular due to the lack of appropriate and robust diagnostic tools. We performed a psychometric validation and diagnostic accuracy study of the French version of the RAADS-R on a sample of 305 adults: 105 with ASD without ID, 99 with psychiatric disorders, and 103 non-psychiatric control groups. The French version of the RAADS-R demonstrates good reliability and diagnostic validity, suggesting that it can help clinicians during the diagnostic process in adults with ASD without ID. However, the finding that a two-factor structure better fits the results requires further validation. This study point out the need of further study of RAADS in psychiatric disorders group due to the relatively high false positive rate (55.6%) of ASD.

School Inclusion in Children and Adolescents with Autism Spectrum Disorders in France: Report from the ELENA French Cohort Study.

Children and adolescents with ASD are increasingly included in regular school settings, however little is known about how placement decisions are made. In the present study, we examined the types and duration of school attendance among children and adolescents in the ELENA Cohort, a multi-center study of children and adolescents with ASD, ages 2-16 years, in France. Results showed that 88% of subjects were attending school and that children and adolescents with more severe adaptive and cognitive deficits were less likely to attend school. The results provide a topography on school inclusion and ASD in France. Challenging behaviors and sensory processing difficulties were associated with partial-inclusion; and co-occurring anxiety symptoms were associated with inclusion on a full-time basis.

The Impact of Atypical Sensory Processing on Adaptive Functioning and Maladaptive Behaviors in Autism Spectrum Disorder During Childhood: Results From the ELENA Cohort.

Atypical sensory processing is common in autism spectrum disorders (ASD), but their role in adaptive difficulties and problem behaviors is poorly understood. Our aim was to determine the prevalence and type of atypical sensory processing in children with ASD and investigate its impact on their adaptive functioning and maladaptive behaviors. We studied a subsample of 197 children rigorously diagnosed with ASD from the ELENA cohort. Children were divided into atypical and typical sensory processing groups and several independent variables were compared, including adaptive functioning and maladaptive behaviors. Overall, 86.8% of the children had at least one atypical sensory pattern and all sensory modalities were disturbed. Atypical sensory processing explained a significant part of the variance of behavioral problems.